Methylene-disalicylic acid derivative



Patented Jan. 14, 1930 i' i UNITED srA'rE s PAT NT oirr ce SAMUEL LEWIS summnns, or-roar WASIEICNGTON, PENNSYLVANIA METHYLENEPDISALICYILIG ncxn DERIVATIVE 1T0 Drawing.

My invention relates to organic compounds and their manufacture and is especially con cerned with the iodination product of the diacetyl derivative of methylene-disalicylamide and its homologues such as hereinafter indicated. These substances (especially the particular one named) are useful for pharmaceutical purposes, as hereinafter indicated,- I v v My productmay be prepared as follows,

though I do not limit myself to this particular method.

Starting with methylene-disalicylic acid, the first step esterification. Various 'homologousesters may be produced; As the ester is converted into the amide in the next main step, the nature of the alcohol used in I')I'B paring the ester is of little consequence, since it does not influence the final product. Dis solve 288 lbs. of methylene-disalicylic acid I in 150lbs. of ethyl alcohol and slowly add I to this a' mixture of 60 lbs. of 66 B', sulphuric acid and 40 lbs. of water, keeping the temperature at or below- 70 C. When this hasall been added the mixture is heated .under a reflux condenser to 150 C., and kept at that temperature for 2 hours. This yields as-the essential product the diethyl ester ofmethylene-disalicylic acid: I I

mnuomcoomui a;

This may be freed from sulphuric *acid and unreacted organic acid by washing with water followed by dilute soda solution. The second main step is to convertthis ester into'the amide, which may be done as follows; 7 I

Heat 3 44'parts of the ethyl ester (or the corresponding amount of anyother ester) of methylene-disalicylic acid with 120 parts This is crystalliiid' iieai'l white in. color soluble in alcohol but insolu 'le water. I

of concentrated aqueous ammonia (28%) in i an autoclave to'110 for 4 hours. The essential product is 'methylene-di'salicylamide,

having the formula: I I

' mmomoorzm Application filed October 12, was. Serial No. 312,202.

I The third main step is to acetylate this amide,-Which may be accomplished asfollows, though I do not limit myself to this method: 286 parts of methylene-disalicylamide are dissolved in 100 parts of glacial acetic acid and 210 parts of acetic anhydride and heated under a reflux condenser for 2 hours. The essential product is the diacetyl derivative of'methylene-disalicylamide:

cuiAococfiecoNm 011/ CaHa(OCOCH:)CONH: Y

This 'is a crystalline substance, insoluble in water, but soluble in alcohol and ether.

The fourthmain step is to iodinate. this allowed to crystallize out. The essential product is an iodine substitution product of diacetyl methylene-disalicylamidehaving the formula: 1 a

01110 cm com:

CH/ I Q9 mmuocooneoonm Thi s is a crystalline compound, practically s5 tasteless, insoluble in water but soluble in alcohol and ether. It is useful as an antiseptic, antineuralgic, antiarthritic and antirheumatic. The dose may befrom to 180 grainsper day'.

' By varying the proportion of iodine and the time of the reaction, more than two I less than two atoms'of iodine may be introduced. The products so obtained are of the n; same eneral nature as the diiodo derivative 'descri ed and are useful forthesamepur- I'Havi'ng thus described my invention, I claim:

L 'The herein described liodin'ation prod '100 ucts of diaeetyl methylene disalicyl amide containing iodine in meta position to the methylene linkage; insoluble in water but soluble in alcohol.

2. The herein described iodination product of diacetyl-methylene-disalicylamide, ins0lu ble in Water but soluble in alcohol, and having the formula: v

ommoooonoooNn, 011/ CaHzHOCOCHDCONH;

In testimony whereof, I have hereunto signed my name at Ambler, Pennsylvania, this 9th day of October, 1928.

SAMUEL LEWIS SUMMERS. 

